Anterior minimally invasive extrapleural retroperitoneal approach to the thoraco-lumbar junction of the spine

SummaryBackgroundThe anterior approach to the thoraco-lumbar junction of the spine allows therapeutic interventions on post-traumatic, infectious, and neoplastic vertebral lesions from T11 to L2 combining spinal cord decompression, corporectomy, and vertebral body fusion. However, this approach also has a reputation for damaging the intervening anatomic structures (lungs, peritoneum, and diaphragm). The objective of this study was to show that both nervous structure decompression and anterior vertebral reconstruction can be achieved via an anterior minimally invasive extrapleural retroperitoneal (AMIER) approach.MaterialWe describe each of the steps of the AMIER approach to the thoraco-lumbar junction of the spine.ResultsThe AMIER approach ensures excellent exposure that allows full decompression and satisfactory anterior anatomic reconstruction. The main difficulties and complications relate to the lungs, and a painstaking and rigorous technique limits the complications compared to conventional thoraco-phreno-lumbotomy

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1693P Incidence of NTRK genes fusion in adult brain tumours: A prospective cohort of 140 patients with cerebral gliomas and brain metastases

International audienceBackground: ImmTAC molecules are TCR-anti-CD3 bispecific fusion proteins that can redirect polyclonal T cell activation against cancer cells. Tebentafusp, a gp100-directed ImmTAC, has demonstrated survival benefit in metastatic uveal melanoma 1. Here, patient-derived tumour organoids (TO) 2 and 3-dimensional multicellular melanospheres were evaluated as tumour models to study ImmTAC activity. Methods: 3D melanospheres were generated by low adherence culture of melanoma cell lines (MEL202, MEL624, 92.1, MP-41, A375, IGR-1, Mewo) and their melanin synthesis genes were quantified by qPCR. The capacity of ImmTAC to redirect T cells against melanospheres was assessed in vitro using IFNg and granzyme B Elispots in the presence or absence of commercially sourced IFNa2 or IFNb. Patient derived TO were generated by Tempus 2 and screened for HLA-A*02:01 and antigen positivity. ImmTAC-mediated killing of relevant TO was assessed by 3D high content imaging. Results: Melanospheres formed from all melanoma cell lines tested, and upregulated melanin synthesis genes including PMEL, MITF, and MLANA. This translated into visible but heterogenous melanin expression. ImmTAC were capable of redirecting T cells against cells from melanospheres to produce IFNg (EC 50 23 pM-4.8 nM) and granzyme B (EC 50 130 pM-1.4 nM). Treatment of 3D cultures with IFNa2 or IFNb for 48 hours augmented ImmTAC-mediated redirection of IFNg secretion by a mean of 4.42-fold. To further assess ImmTAC-mediated T cell redirection against more complex in vitro cultures, TO were derived from patient tumours and co-cultured with PBMC for 96 hours. In these settings, clinically relevant doses of ImmTAC redirected T cells to induce cell lysis of antigen positive TO (EC 50 29.3 pM). Conclusions: 3D melanospheres and TO may provide useful models to study tumour biology, heterogeneity, and ImmTAC activity. ImmTAC were capable of redirecting T cells against these in vitro tumour models, which will allow for better understanding of mechanism of action. 1

Molecular profile of androgen-independent prostate cancer xenograft LuCaP 23.1

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